The overall goal of this proposal is to elucidate the neural bases of emotional reactivity and cognitive regulation in social phobia (SP), and to identify the neural mechanisms underlying therapeutic change associated with cognitive-behavioral therapy (CBT) for SP. Basic research has examined emotional reactivity and cognitive regulation in healthy controls (HC), but this research has not yet delineated the mechanisms underlying emotion regulation in individuals with SP. Clinical research has shown that CBT is an effective treatment for many individuals with SP, but mechanisms of change and predictors of therapeutic response are not yet well described. To integrate basic and clinical literatures, we use a framework that views emotion regulation in terms of interactions between ventral emotion-generative brain regions and dorsal emotion- regulatory brain regions. Within this framework, we propose to examine emotional reactivity and cognitive regulation in HC and in participants with generalized SP pre- and post-CBT. The proposed studies address 3 aims: Aim 1 examines the neural substrates of emotional reactivity and cognitive regulation in SP versus HC. Study 1A tests the hypothesis that SP individuals will show greater responses than HC in ventral emotion-generative brain regions to social anxiety stimuli, but comparable responses to (non-social) general anxiety or neutral stimuli. Study 1B tests the hypothesis that SP individuals will show lesser responses than HC in dorsal emotion-regulatory brain regions when asked to regulate responses to social anxiety stimuli, but comparable responses when asked to regulate responses to general anxiety stimuli. Aim 2 identifies mechanisms of change by examining SP patients pre- and post-CBT. SP patients who complete Studies 1A and 1B will undergo 4 months of CBT. Upon completion of treatment or waitlist (SP) or a matched time interval (HC), Study 2A tests the hypothesis that SP CBT responders will show lesser responses in ventral brain regions to social anxiety stimuli (a) than at pre-treatment, (b) than SP non-responders at post-CBT, and (c) than SP waitlist controls. Study 2B tests the hypothesis that CBT responders will show greater responses in dorsal brain regions to social anxiety stimuli (a) than at pre-treatment, (b) than SP non-responders at post- treatment, and (c) than SP waitlist controls. For both study 2A and 2B, we expect that SP CBT responders and HC at Time 2 will show comparable responses to social and general anxiety stimuli. Aim 3 assesses predictors of treatment responses to CBT. Study 3 tests the hypothesis that greater emotional reactivity (affective vulnerability) and lesser cognitive regulation (implementation deficit) pre- and post-treatment will independently predict worse clinical outcomes at 5 and 10 months post-CBT for individuals with SP. The broad, long-term objective of this translational research program is to contribute to advances in theory and clinical interventions that will improve psychological well-being in people suffering from SP. [unreadable] [unreadable] [unreadable]